title: Does packaging with a calendar feature improve adherence to self-administered medication for long-term use? A systematic review.
abstract: BACKGROUND
  The therapeutic benefit of self-administered medications for long-term use is limited by an average 50% nonadherence rate. Patient forgetfulness is a common factor in unintentional nonadherence. Unit-of-use packaging that incorporates a simple day-and-date feature (calendar packaging) is designed to improve adherence by prompting patients to maintain the prescribed dosing schedule.
  
  
  OBJECTIVE
  To review systematically, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, randomized controlled trial evidence of the adherence benefits and harms of calendar blister packaging (CBP) and calendar pill organizers (CPO) for self-administered, long-term medication use.
  
  
  METHODS
  Data sources included the MEDLINE and Web of Science and Cochrane Library databases from their inception to September 2010 and communication with researchers in the field. Key search terms included blister-calendar pack, blister pack, drug packaging, medication adherence, medication compliance, medication compliance devices, medication containers, medication organizers, multicompartment compliance aid, persistence, pill-box organizers, prescription refill, randomized controlled trials, and refill compliance. Selected studies had an English-language title; a randomized controlled design; medication packaged in CBP or CPO; a requirement of solid, oral medication self-administered daily for longer than 1 month in community-dwelling adults; and at least 1 quantitative outcome measure of adherence. Two reviewers extracted data independently on study design, sample size, type of intervention and control, and outcomes.
  
  
  RESULTS
  Ten trials with a total of 1045 subjects met the inclusion criteria, and 9 also examined clinical outcomes (seizures, blood pressure, psychiatric symptoms) or health care resource utilization. Substantial heterogeneity among trials precluded meta-analysis. In 3 studies, calendar packaging was part of a multicomponent adherence intervention. Six of 10 trials reported higher adherence, but it was associated with clinically significant improvement in only 1 study: 50% decreased seizure frequency with a CPO-based, multicomponent intervention. No study reported sufficient information to examine conclusively potential harms related to calendar packaging.
  
  
  CONCLUSIONS
  All trials had significant methodological limitations, such as inadequate randomization or blinding, or reported insufficient information regarding enrolled subjects and attrition, which resulted in a moderate-to-high risk of bias and, in 2 studies, unevaluable outcome data. Trials were generally short and sample sizes small, with heterogeneous adherence outcome measures.
  
  
  CONCLUSIONS
  Calendar packaging, especially in combination with education and reminder strategies, may improve medication adherence. Methodological limitations preclude definitive conclusions about the effect size of adherence and clinical benefits or harms associated with CBP and CPO. High-quality trials of adequate size and duration are needed to assess the clinical effectiveness of such interventions.
authors.affiliation: Venebio, LLC, Richmond, Virginia 23225, USA. barb.zedler@venebio.com
authors.forename: Barbara K
authors.initials: BK
authors.lastname: Zedler
authors.forename: Priyanka
authors.initials: P
authors.lastname: Kakad
authors.forename: Susan
authors.initials: S
authors.lastname: Colilla
authors.forename: Lenn
authors.initials: L
authors.lastname: Murrelle
authors.forename: Nirav R
authors.initials: NR
authors.lastname: Shah
mesh_terms: D000328:Adult; D004349:Drug Packaging; D006801:Humans; D004364:Pharmaceutical Preparations / Q000008:administration & dosage; D016032:Randomized Controlled Trials as Topic; D017010:Reminder Systems; D012646:Self Administration; D013997:Time Factors; D016903:Drug Monitoring
chemical_list: D004364:Pharmaceutical Preparations